tbuckley/cabot-search huggingface dataset:
HycDemux: a hybrid unsupervised approach for accurate barcoded sample demultiplexing in nanopore sequencing
Authors: Renmin Han, Junhai Qi, Yang Xue, Xiujuan Sun, Fa Zhang, Xin Gao, Guojun Li
Journal: Genome biology (2023)

Abstract DNA barcodes enable Oxford Nanopore sequencing to sequence multiple barcoded DNA samples on a single flow cell. DNA sequences with the same barcode need to be grouped together through demultiplexing. As the number of samples increases, accurate demultiplexing becomes difficult. We introduce HycDemux, which incorporates a GPU-parallelized hybrid clustering algorithm that uses nanopore signals and DNA sequences for accurate data clustering, alongside a voting-based module to finalize the demultiplexing results. Comprehensive experiments demonstrate that our approach outperforms unsupervised tools in short sequence fragment clustering and performs more robustly than current state-of-the-art demultiplexing tools for complex multi-sample sequencing data.
Genomic variant benchmark: if you cannot measure it, you cannot improve it
Authors: Sina Majidian, Daniel Paiva Agustinho, Chen-Shan Chin, Fritz J. Sedlazeck, Medhat Mahmoud
Journal: Genome biology (2023)

Abstract Genomic benchmark datasets are essential to driving the field of genomics and bioinformatics. They provide a snapshot of the performances of sequencing technologies and analytical methods and highlight future challenges. However, they depend on sequencing technology, reference genome, and available benchmarking methods. Thus, creating a genomic benchmark dataset is laborious and highly challenging, often involving multiple sequencing technologies, different variant calling tools, and laborious manual curation. In this review, we discuss the available benchmark datasets and their utility. Additionally, we focus on the most recent benchmark of genes with medical relevance and challenging genomic complexity.
Large sample size and nonlinear sparse models outline epistatic effects in inflammatory bowel disease
Authors: Nora Verplaetse, Antoine Passemiers, Adam Arany, Yves Moreau, Daniele Raimondi
Journal: Genome biology (2023)

Abstract Background Despite clear evidence of nonlinear interactions in the molecular architecture of polygenic diseases, linear models have so far appeared optimal in genotype-to-phenotype modeling. A key bottleneck for such modeling is that genetic data intrinsically suffers from underdetermination ( $$p \gg n$$ <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"> <mml:mrow> <mml:mi>p</mml:mi> <mml:mo>≫</mml:mo> <mml:mi>n</mml:mi> </mml:mrow> </mml:math> ). Millions of variants are present in each individual while the collection of large, homogeneous cohorts is hindered by phenotype incidence, sequencing cost, and batch effects. Results We demonstrate that when we provide enough training data and control the complexity of nonlinear models, a neural network outperforms additive approaches in whole exome sequencing-based inflammatory bowel disease case–control prediction. To do so, we propose a biologically meaningful sparsified neural network architecture, providing empirical evidence for positive and negative epistatic effects present in the inflammatory bowel disease pathogenesis. Conclusions In this paper, we show that underdetermination is likely a major driver for the apparent optimality of additive modeling in clinical genetics today.
Monoclonal antibodies lock down SARS-CoV-2 spike
Authors: Hsiang-Chi Huang, Davide Angeletti
Journal: Trends in Immunology (2023)

SARS-CoV-2 rapidly accumulated mutations in its immunodominant receptor-binding domain (RBD), rendering all clinically authorized monoclonal antibodies (mAbs) ineffective. Liu et al. unveil potent human mAbs that neutralize all tested SARS-CoV-2 variants by locking the Spike protein RBD in a downward conformation, thus inhibiting receptor engagement.
Recompensation in cirrhosis: unravelling the evolving natural history of nonalcoholic fatty liver disease
Authors: Gong Feng, Luca Valenti, Vincent Wai-Sun Wong, Yasser Mahrous Fouad, Yusuf Yilmaz, Won Kim, Giada Sebastiani, Zobair M. Younossi, Virginia Hernandez-Gea, Ming-Hua Zheng
Journal: Nature Reviews Gastroenterology & Hepatology (2023)
Seeing social interactions
Authors: Emalie McMahon, Leyla Isik
Journal: Trends in Cognitive Sciences (2023)

Seeing the interactions between other people is a critical part of our everyday visual experience, but recognizing the social interactions of others is often considered outside the scope of vision and grouped with higher-level social cognition like theory of mind. Recent work, however, has revealed that recognition of social interactions is efficient and automatic, is well modeled by bottom-up computational algorithms, and occurs in visually-selective regions of the brain. We review recent evidence from these three methodologies (behavioral, computational, and neural) that converge to suggest the core of social interaction perception is visual. We propose a computational framework for how this process is carried out in the brain and offer directions for future interdisciplinary investigations of social perception.
TIM-3 blockade in diffuse intrinsic pontine glioma models promotes tumor regression and antitumor immune memory
Authors: Iker Ausejo-Mauleon, Sara Labiano, Daniel de la Nava, Virginia Laspidea, Marta Zalacain, Lucía Marrodán, Marc García-Moure, Marisol González-Huarriz, Irati Hervás-Corpión, Laasya Dhandapani, Silvestre Vicent, Maria Collantes, Iván Peñuelas, Oren J. Becher, Mariella G. Filbin, Li Jiang, Jenna Labelle, Carlos A.O. de Biagi-Junior, Javad Nazarian, Sandra Laternser, Timothy N. Phoenix, Jasper van der Lugt, Mariette Kranendonk, Raoull Hoogendijk, Sabine Mueller, Carlos De Andrea, Ana C. Anderson, Elizabeth Guruceaga, Carl Koschmann, Viveka Nand Yadav, Jaime Gállego Pérez-Larraya, Ana Patiño-García, Fernando Pastor, Marta M. Alonso
Journal: Cancer Cell (2023)

Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain stem tumor and the leading cause of pediatric cancer-related death. To date, these tumors remain incurable, underscoring the need for efficacious therapies. In this study, we demonstrate that the immune checkpoint TIM-3 (HAVCR2) is highly expressed in both tumor cells and microenvironmental cells, mainly microglia and macrophages, in DIPG. We show that inhibition of TIM-3 in syngeneic models of DIPG prolongs survival and produces long-term survivors free of disease that harbor immune memory. This antitumor effect is driven by the direct effect of TIM-3 inhibition in tumor cells, the coordinated action of several immune cell populations, and the secretion of chemokines/cytokines that create a proinflammatory tumor microenvironment favoring a potent antitumor immune response. This work uncovers TIM-3 as a bona fide target in DIPG and supports its clinical translation.
Catalysing multi-stakeholder collaboration to tackle climate-related health emergencies in Africa
Authors: Magaran Monzon Bagayoko
Journal: BMJ (2023)

scientist and WHO representative to Gabon Today, the negative impact of climate change on health and wellbeing is undeniable. 1 -3 Nowhere is this anticipated to have greater impact than in Africa, lower income countries, and small island developing states where social, political, environmental, and economic conditions already create serious health vulnerabilities. 4 -6 Of the nearly 2000 public health events recorded in the African region between 2001 and 2021, 56% were climate related, with 25% more events recorded in the past decade compared with the previous one. 7These include waterborne and vector-borne disease emergencies such as cholera, malaria, and arbovirosis.
To tackle the climate crisis, we need to transform systems according to ancestral original instructions
Authors: Rhys Jones
Journal: BMJ (2023)

In Aotearoa (contemporary Māori language name for New Zealand) we've tended to view ourselves as relatively protected from the health impacts of the climate crisis, but earlier this year that complacency came face to face with reality.Floods and storms hit Te Ika-a-Māui, the North Island, leading to loss of life and major social, economic, and environmental upheaval.These extreme weather events triggered a public health crisis with serious and profoundly inequitable effects, while also serving as a warning of worse to come.
Increasing Use of Shorter-Course Radiotherapy for Prostate Cancer
Authors: James B. Yu, Yilun Sun, Angela Y. Jia, Randy A. Vince, Jonathan E. Shoag, Nicholas G. Zaorsky, Daniel E. Spratt
Journal: JAMA Oncology (2023)

Randomized clinical trials have demonstrated the noninferiority of shorter radiotherapy (RT) courses (termed hypofractionation) compared with longer RT courses in patients with localized prostate cancer. Although shorter courses are associated with cost-effectiveness, convenience, and expanded RT access, their adoption remains variable.
Leveraging the Expertise of the CTSA Program to Increase the Impact and Efficiency of Clinical Trials
Authors: Paul A. Harris, Sarah E. Dunsmore, Jane C. Atkinson, Daniel Kelly Benjamin, Gordon R. Bernard, J. Michael Dean, Jamie P. Dwyer, Daniel E. Ford, Harry P. Selker, Salina P. Waddy, Kenneth L. Wiley, Consuelo H. Wilkins, Sarah K. Cook, Jeri S. Burr, Terri L. Edwards, Jacqueline Huvane, Nan Kennedy, Karen Lane, Ryan Majkowski, Sarah Nelson, Marisha E. Palm, Mary Stroud, Dixie D. Thompson, Linda Busacca, Mitchell S. V. Elkind, Robert P. Kimberly, Muredach P. Reilly, Daniel F. Hanley, Rachel Greenberg, Kanecia Zimmerman, Brian Smith, Frank Rockhold, Lori Poole, Jesse Hickerson, Eilene Pham, Eve Marion, Helen Boyle, Vincent Miller, Sonya Sutton, Michelle Jones, Princess Abbott-Grimes, Nichole McBee, Andrew Mould, Lindsay Eyzaguirre, Megan Singleton, Janelle Maddox-Regis, Shannon Hillery, Angeline Nanni, Meghan Hildreth, Cecilia Pessoa-Gingerish, Emily Bartlett, Theodora Cohen, Cortney Wieber, Krista Vermillion, Erin Rothwell, Kevin Watt, Kathy Sward, John M. VanBuren, Mary Pautler, Marie Kay, Jordan Bridges, Krista Ellis, Francis Sebahar, Eun Hea Unsicker, Valeriya Vasenina, Talmage Morris, Michelle Aponte, Ann Johnson, Annie Risenmay, Lisa Rigtrup, Gary Henderson, Ammon Leon Pate, Monse Lopez, Leslie Boone, Loretta Byrne, Tara Helmer, Maeve Tischbein, Leah Dunkel, Stephanie Mayers, Kaysi Quarles, Jasmine Bell, Bridget Swindell, Jabari Ichimura, Devan Ray, Caitlin Rantala, Jessica Eidenmuller, Emily Serdoz, Natalie Dilts, David Crenshaw, Brooklyn Henderson, Meghan Vance, Delicia Burts, Dione Grant, Jahi Hamilton, Matt Schorr, Colleen Lawrence, Meredith Bernui, Taylor Budine, Amna Baig, Joseph Christodoulou, Jodie Cohen, Tiffany Chen, Julia Dunagan, Wendy Lloyd
Journal: JAMA Network Open (2023)

Multicenter clinical trials play a critical role in the translational processes that enable new treatments to reach all people and improve public health. However, conducting multicenter randomized clinical trials (mRCT) presents challenges. The Trial Innovation Network (TIN), established in 2016 to partner with the Clinical and Translational Science Award (CTSA) Consortium of academic medical institutions in the implementation of mRCTs, consists of 3 Trial Innovation Centers (TICs) and 1 Recruitment Innovation Center (RIC). This unique partnership has aimed to address critical roadblocks that impede the design and conduct of mRCTs, in expectation of accelerating the translation of novel interventions to clinical practice. The TIN's challenges and achievements are described in this article, along with examples of innovative resources and processes that may serve as useful models for other clinical trial networks providing operational and recruitment support.
A Prospective Study Exploring the Safety and Efficacy of Lenvatinib for Patients with Advanced Hepatocellular Carcinoma and High Tumor Burden: The LAUNCH Study
Authors: Kazufumi Kobayashi, Sadahisa Ogasawara, Susumu Maruta, Tomomi Okubo, Norio Itokawa, Yuki Haga, Yuya Seko, Michihisa Moriguchi, Shunji Watanabe, Yuki Shiko, Hirokazu Takatsuka, Hiroaki Kanzaki, Keisuke Koroki, Masanori Inoue, Masato Nakamura, Soichiro Kiyono, Naoya Kanogawa, Takayuki Kondo, Eiichiro Suzuki, Yoshihiko Ooka, Shingo Nakamoto, Yosuke Inaba, Masafumi Ikeda, Shinichiro Okabe, Naoki Morimoto, Yoshito Itoh, Kazuyoshi Nakamura, Kenji Ito, Ryosaku Azemoto, Masanori Atsukawa, Ei Itobayashi, Naoya Kato
Journal: Clinical Cancer Research (2023)

Abstract Purpose: This study aimed to investigate the safety and efficacy of lenvatinib in real-world settings, including patients excluded from the REFLECT trial, a phase III trial that compared lenvatinib with sorafenib. Patients and Methods: This multicenter, nonrandomized, open-label prospective study was conducted at 10 medical facilities in Japan (jRCTs031190017). Eligible patients had advanced hepatocellular carcinoma (HCC) and were suitable for lenvatinib therapy. The study included patients with high tumor burden (with &amp;gt;50% intrahepatic tumor volume, main portal vein invasion, or bile duct invasion), Child-Pugh B status, and receiving lenvatinib as second-line therapy following atezolizumab plus bevacizumab. Results: From December 2019 to September 2021, 59 patients were analyzed (47 and 12 patients with Child-Pugh A and B, respectively). In patients with Child-Pugh A, the frequency of aspartate aminotransferase elevation was high (72.7%) in the high-burden group. No other significant ad verse events (AE) were observed even in second-line treatment. However, patients with Child-Pugh B had high incidence of grade ≥3 AE (100.0%) and high discontinuation rates caused by AE (33.3%) compared with patients with Child-Pugh A (80.9% and 17.0%, respectively). Median progression-free survival was 6.4 and 2.5 months and median overall survival was 19.7 and 4.1 months in Child-Pugh A and B, respectively. Lenvatinib plasma concentration was higher in patients with Child-Pugh B on days 8 and 15 and correlated with dose modifications and lower relative dose intensity. Conclusions: Lenvatinib is safe and effective for advanced HCC in patients with Child-Pugh A, even with high tumor burden. However, it carries a higher risk of AE and may not provide adequate efficacy for patients with Child-Pugh B status.
Raised lesions on the ankles
Authors: Guillaume Dejonckheere, Mathieu Daoud, Jonathan M White
Journal: BMJ (2023)

A man in his 40s presented with a five year history of two painless, gradually enlarging, hyperkeratotic lesions on the lateral sides of the ankles (fig 1).He reported praying for approximately 50 minutes each day.The prayer posture involved kneeling and sitting on the dorsolateral aspect of the ankles.His feet were positioned parallel to each other, slightly apart, with weight equally distributed on both feet to maintain stability.
Cooperative CAR targeting to selectively eliminate AML and minimize escape
Authors: Sascha Haubner, Jorge Mansilla-Soto, Sarah Nataraj, Friederike Kogel, Qing Chang, Elisa de Stanchina, Michael Lopez, Mei Rosa Ng, Kathryn Fraser, Marion Subklewe, Jae H. Park, Xiuyan Wang, Isabelle Rivière, Michel Sadelain
Journal: Cancer Cell (2023)

Acute myeloid leukemia (AML) poses a singular challenge for chimeric antigen receptor (CAR) therapy owing to its phenotypic heterogeneity and similarity to normal hematopoietic stem/progenitor cells (HSPCs). Here we expound a CAR strategy intended to efficiently target AML while minimizing HSPC toxicity. Quantification of target expression in relapsed/refractory patient samples and normal HSPCs reveals a therapeutic window for gated co-targeting of ADGRE2 and CLEC12A: We combine an attenuated ADGRE2-CAR with a CLEC12A-chimeric costimulatory receptor (ADCLEC.syn1) to preferentially engage ADGRE2posCLEC12Apos leukemic stem cells over ADGRE2lowCLEC12Aneg normal HSPCs. ADCLEC.syn1 prevents antigen escape in AML xenograft models, outperforms the ADGRE2-CAR alone and eradicates AML despite proximate myelopoiesis in humanized mice. Off-target HSPC toxicity is similar to that of a CD19-CAR and can be mitigated by reducing CAR T cell-derived interferon-γ. Overall, we demonstrate the ability of target density-adapted cooperative CAR targeting to selectively eliminate AML and potentially obviate the need for hematopoietic rescue.
Berdazimer gel for molluscum contagiosum: An integrated analysis of 3 randomized controlled trials
Authors: Jeffrey L. Sugarman, Adelaide Hebert, John C. Browning, Amy S. Paller, Stephen Stripling, Lawrence J. Green, Martina Cartwright, Carolyn Enloe, Nick Wells, Tomoko Maeda-Chubachi
Journal: Journal of the American Academy of Dermatology (2023)

<h3>Background</h3> An out-of-office therapeutic agent indicated for molluscum contagiosum is needed. <h3>Objective</h3> To assess the efficacy and safety of berdazimer gel, 10.3% (a topical, antiviral, nitric oxide–releasing medication) versus vehicle. <h3>Methods</h3> Berdazimer gel, 10.3% or vehicle was applied once daily to all molluscum contagiosum lesions for 12 weeks in patients ≥6 months with 3-70 mollusca. Efficacy assessment: complete lesion clearance and partial clearance at week 12. Safety and tolerability assessment: adverse events through week 24 and local skin reactions through week 12. <h3>Results</h3> There were 1598 patients enrolled (<i>n</i> = 917 berdazimer, <i>n</i> = 681 vehicle). Berdazimer was superior to vehicle at week 12 in complete clearance rates, 30.0% versus 19.8% (odds ratio, 1.75; 95% CI, 1.38-2.23, <i>P</i> < .001). Subgroup analyses of primary efficacy showed consistent favorable efficacy for berdazimer across most subgroups, including age, sex, baseline lesion count, and disease duration. Berdazimer provided favorable outcome for partial clearance. Application-site pain (18.7% vs 4.8% in berdazimer vs vehicle) and erythema (11.7% vs 1.3%), mostly mild to moderate, were the most common local skin reactions. <h3>Limitations</h3> <b>B</b>erdazimer <b>s</b>odium <b>i</b>n <b>m</b>olluscum <b>p</b>atients with <b>le</b>sions (B-SIMPLE) trials enrolled only US patients; no efficacy assessments beyond week 12. <h3>Conclusions</h3> Berdazimer gel, 10.3% showed favorable efficacy and safety across subgroups.
Disease Severity of Respiratory Syncytial Virus Compared with COVID-19 and Influenza Among Hospitalized Adults Aged ≥60 Years — IVY Network, 20 U.S. States, February 2022–May 2023
Authors: Diya Surie, Katharine A. Yuengling, Jennifer DeCuir, Yuwei Zhu, Manjusha Gaglani, Adit A. Ginde, H. Keipp Talbot, Jonathan D. Casey, Nicholas M. Mohr, Shekhar Ghamande, Kevin W. Gibbs, D. Clark Files, David N. Hager, Harith Ali, Matthew E. Prekker, Michelle N. Gong, Amira Mohamed, Nicholas J. Johnson, Jay S. Steingrub, Ithan D. Peltan, Samuel M. Brown, Aleda M. Leis, Akram Khan, Catherine L. Hough, William S. Bender, Abhijit Duggal, Jennifer G. Wilson, Nida Qadir, Steven Y. Chang, Christopher Mallow, Jennie H. Kwon, Matthew C. Exline, Adam S. Lauring, Nathan I. Shapiro, Cristie Columbus, Ivana A. Vaughn, Mayur Ramesh, Basmah Safdar, Natasha Halasa, James D. Chappell, Carlos G. Grijalva, Adrienne Baughman, Todd W. Rice, Kelsey N. Womack, Jin H. Han, Sydney A. Swan, Indrani Mukherjee, Nathaniel M. Lewis, Sascha Ellington, Meredith L. McMorrow, Emily T. Martin, Wesley H. Self
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

On June 21, 2023, CDC's Advisory Committee on Immunization Practices recommended respiratory syncytial virus (RSV) vaccination for adults aged ≥60 years, offered to individual adults using shared clinical decision-making.Informed use of these vaccines requires an understanding of RSV disease severity.To characterize RSV-associated severity, 5,784 adults aged ≥60 years hospitalized with acute respiratory illness and laboratory-confirmed RSV, SARS-CoV-2, or influenza infection were prospectively enrolled from 25 hospitals in 20 U.S. states during February 1, 2022-May 31, 2023.Multivariable logistic regression was used to compare RSV disease severity with COVID-19 and influenza severity on the basis of the following outcomes: 1) standard flow (<30 L/minute) oxygen therapy, 2) high-flow nasal cannula (HFNC) or noninvasive ventilation (NIV), 3) intensive care unit (ICU) admission, and 4) invasive mechanical ventilation (IMV) or death.Overall, 304 (5.3%) enrolled adults were hospitalized with RSV, 4,734 (81.8%) with COVID-19 and 746 (12.9%) with influenza.Patients hospitalized with RSV were more likely to receive standard flow oxygen, HFNC or NIV, and ICU admission than were those hospitalized with COVID-19 or influenza.Patients hospitalized with RSV were more likely to receive IMV or die compared with patients hospitalized with influenza (adjusted odds ratio = 2.08; 95% CI = 1.33-3.26).Among hospitalized older adults, RSV was less common, but was associated with more severe disease than COVID-19 or influenza.High disease severity in older adults hospitalized with RSV is important to consider in shared clinical decision-making regarding RSV vaccination.
Characteristics and Outcomes Among Adults Aged ≥60 Years Hospitalized with Laboratory-Confirmed Respiratory Syncytial Virus — RSV-NET, 12 States, July 2022–June 2023
Authors: Fiona P. Havers, Michael Whitaker, Michael Melgar, Bhoomija Chatwani, Shua J. Chai, Nisha B. Alden, James Meek, Kyle P. Openo, Patricia A. Ryan, Sue Kim, Ruth Lynfield, Yomei P. Shaw, Grant Barney, Brenda L. Tesini, Melissa Sutton, H. Keipp Talbot, Kristen P. Olsen, Monica E. Patton, Pam Daily Kirley, Elizabeth Austin, Daewi Kim, Chandler Surell, Maya Monroe, Lauren Leegwater, Erica Mumm, Molly Bleecker, Adam Rowe, Kevin Popham, Arilene Novak, William Schaffner, Holly Staten
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults.In May 2023, two RSV vaccines were approved for prevention of RSV lower respiratory tract disease in adults aged ≥60 years.In June 2023, CDC recommended RSV vaccination for adults aged ≥60 years, using shared clinical decision-making.Using data from the Respiratory Syncytial Virus-Associated Hospitalization Surveillance Network, a population-based hospitalization surveillance system operating in 12 states, this analysis examined characteristics (including age, underlying medical conditions, and clinical outcomes) of 3,218 adults aged ≥60 years who were hospitalized with laboratory-confirmed RSV infection during July 2022-June 2023.Among a random sample of 1,634 older adult patients with RSV-associated hospitalization, 54.1% were aged ≥75 years, and the most common underlying medical conditions were obesity, chronic obstructive pulmonary disease, congestive heart failure, and diabetes.Severe outcomes occurred in 18.5% (95% CI = 15.9%-21.2%) of hospitalized patients aged ≥60 years.Overall, 17.0% (95% CI = 14.5%-19.7%) of patients with RSV infection were admitted to an intensive care unit, 4.8% (95% CI = 3.5%-6.3%)required mechanical ventilation, and 4.7% (95% CI = 3.6%-6.1%)died; 17.2% (95% CI = 14.9%-19.8%) of all cases occurred in long-term care facility residents.These data highlight the importance of prioritizing those at highest risk for severe RSV disease and suggest that clinicians and patients consider age (particularly age ≥75 years), long-term care facility residence, and underlying medical conditions, including chronic obstructive pulmonary disease and congestive heart failure, in shared clinical decisionmaking when offering RSV vaccine to adults aged ≥60 years.
Control of the antitumour activity and specificity of CAR T cells via organic adapters covalently tethering the CAR to tumour cells
Authors: Alexey V. Stepanov, Jia Xie, Qiaoqiao Zhu, Zuyuan Shen, Wenji Su, Letian Kuai, Richard Soll, Christoph Rader, Geramie Shaver, Lacey Douthit, Ding Zhang, Roman Kalinin, Xiang Fu, Yingying Zhao, Tian Qin, Phil S. Baran, Alexander G. Gabibov, David Bushnell, Dario Neri, Roger D. Kornberg, Richard A. Lerner
Journal: Nature Biomedical Engineering (2023)